The controlled release of a therapeutic agent is a central premise of medicine. The controlled release over time of a pharmaceutical drug is a recognized, if not completely predictable, technology that is available in numerous drugs currently on the market. While, controlled release often indicates the release of a compound over a period of time, e.g. the time release of a chemical compound, controlled release can also indicate the release of a compound at a specific location, e.g. drug delivery. Coated stent technology is an example of the delivery of a drug to the arterial area near the stent.
However, in contrast to the time release of simple chemical compounds or delivery of a drug in from a stent, the controlled release of recombinant proteins in vivo via injectable delivery vehicles remains a central challenge in drug delivery. PLGA-based injectable delivery vehicles for model proteins and peptides have been developed, but these delivery vehicles have not been able to deliver recombinant proteins because of their scarcity and fragility. As medicine continues to develop recombinant proteins for therapeutic uses, there will remain a need for delivery of those compounds.
Injectable hydrogels have been considered as a method for delivering drugs to a biological system. Hydrogels are composed of mutually reactive precursors that react in situ to form networks with high water content, mimicking mechanical and chemical properties of surrounding tissues. By varying the concentrations and chemical properties of the soluble precursors, mesh size, degradation times, mechanical properties and release rates of therapeutic agents might be controlled. Although various materials have been used to form synthetic injectable hydrogels, by far the most widely studied gels are those formed from macromolecular poly(ethylene glycol) (PEG) precursors. Numerous free radical polymerization mechanisms have been employed to generate hydrogel networks from soluble PEG-based precursors, but the initiators and free radicals produced during polymerization have the potential to damage the encapsulated therapeutic agents and surrounding tissues. Thus there remains a need to develop injectable hydrogels that are compatible with in vivo uses.